Origin of endothelial progenitors in human postnatal bone marrow

TLDR

This in vitro model of preangioblast‑to‑endothelium differentiation should prove very useful in studying commitment to the angioblast and beyond. In vitro, MAPCs cultured with VEGF differentiate into CD34+, VE‑cadherin+, Flk1+ cells—a phenotype expected for angioblasts. The study shows that CD34–, VE‑cadherin–, AC133+, Flk1+ multipotent adult progenitor cells from postnatal bone marrow differentiate into angioblasts and mature endothelial cells, contribute to tumor and wound neoangiogenesis, and can be expanded over 80 doublings without senescence, making them a promising source for angiogenic therapies.

Abstract

This study demonstrates that a CD34–, vascular endothelial cadherin– (VE-cadherin–), AC133+, and fetal liver kinase+ (Flk1+) multipotent adult progenitor cell (MAPC) that copurifies with mesenchymal stem cells from postnatal human bone marrow (BM) is a progenitor for angioblasts. In vitro, MAPCs cultured with VEGF differentiate into CD34+, VE-cadherin+, Flk1+ cells — a phenotype that would be expected for angioblasts. They subsequently differentiate into cells that express endothelial markers, function in vitro as mature endothelial cells, and contribute to neoangiogenesis in vivo during tumor angiogenesis and wound healing. This in vitro model of preangioblast-to-endothelium differentiation should prove very useful in studying commitment to the angioblast and beyond. In vivo, MAPCs can differentiate in response to local cues into endothelial cells that contribute to neoangiogenesis in tumors. Because MAPCs can be expanded in culture without obvious senescence for more than 80 population doublings, they may be an important source of endothelial cells for cellular pro- or anti-angiogenic therapies.